Hamostaseologie 2020; 40(03): 292-300
DOI: 10.1055/a-1174-1290
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Management of Anticoagulant Treatment and Anticoagulation-Related Complications in Nonagenarians

Michela Giustozzi
1   Internal Vascular and Emergency Medicine and Stroke Unit, University of Perugia, Perugia, Italy
,
Lana A. Castellucci
2   Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
,
Geoffrey D. Barnes
3   Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
› Author Affiliations
Further Information

Publication History

02 February 2020

07 May 2020

Publication Date:
29 July 2020 (online)

Abstract

Given the aging population, the burden of age-dependent diseases is growing. Despite this, elderly patients are often underrepresented in clinical trials and little data are available on current anticoagulant management and outcomes in this unique population, especially those aged 90 years or older. There is uncertainty, and a fear of “doing harm,” that often leads to de-prescription of antithrombotic agents in nonagenarian patients. Decision-making concerning the use of anticoagulant treatment needs to balance the risk of thrombotic events against the risk of major bleeding, especially intracranial hemorrhage. In this perspective, the development of direct oral anticoagulants (DOACs), acting as direct and selective inhibitors of a specific step or enzyme of the coagulation cascade, has dramatically changed oral anticoagulant treatment. In fact, given the lower incidence of intracranial hemorrhage, the favorable overall efficacy and safety, and the lack of routine monitoring, DOACs are the currently recommended anticoagulant agents for the treatment of both atrial fibrillation and venous thromboembolism even in very elderly patients. However, given the limited data available on the management of anticoagulation in nonagenarians, a few unanswered questions remain. In this review, we focused on recent evidence for anticoagulant treatment in atrial fibrillation and venous thromboembolism along with management of anticoagulation-related bleeding in nonagenarians.

 
  • References

  • 1 Foreman KJ, Marquez N, Dolgert A. , et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet 2018; 392 (10159): 2052-2090
  • 2 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 2016; 18 (11) 1609-1678
  • 3 Go AS, Hylek EM, Phillips KA. , et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285 (18) 2370-2375
  • 4 O'Mahony D, Gallagher PF. Inappropriate prescribing in the older population: need for new criteria. Age Ageing 2008; 37 (02) 138-141
  • 5 Mant J, Hobbs FD, Fletcher K. , et al; BAFTA Investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370 (9586): 493-503
  • 6 Connolly SJ, Eikelboom J, Joyner C. , et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364 (09) 806-817
  • 7 Patti G, Lucerna M, Pecen L. , et al. Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strategies in very elderly patients with atrial fibrillation: a sub-analysis from the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J Am Heart Assoc 2017; 6 (07) e005657
  • 8 Shah SJ, Singer DE, Fang MC, Reynolds K, Go AS, Eckman MH. Net clinical benefit of oral anticoagulation among older adults with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2019; 12 (11) e006212
  • 9 Granger CB, Alexander JH, McMurray JJ. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
  • 10 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
  • 11 Patel MR, Mahaffey KW, Garg J. , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
  • 12 Giugliano RP, Ruff CT, Braunwald E. , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
  • 13 Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis. Circulation 2015; 132 (03) 194-204
  • 14 Andreotti F, Rocca B, Husted S. , et al; ESC Thrombosis Working Group. Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J 2015; 36 (46) 3238-3249
  • 15 Giustozzi M, Vedovati MC, Verso M. , et al. Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: a multicentre observational study. Int J Cardiol 2019; 281: 56-61
  • 16 Chao TF, Liu CJ, Lin YJ. , et al. Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation 2018; 138 (01) 37-47
  • 17 Gafoor S, Franke J, Bertog S. , et al. Left atrial appendage occlusion in octogenarians: short-term and 1-year follow-up. Catheter Cardiovasc Interv 2014; 83 (05) 805-810
  • 18 Cruz-González I, Ince H, Kische S. , et al. Left atrial appendage occlusion in patients older than 85 years. Safety and efficacy in the EWOLUTION registry. Rev Esp Cardiol (Engl Ed) 2020; 73 (01) 21-27
  • 19 Spencer FA, Gore JM, Lessard D. , et al. Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost 2008; 100 (05) 780-788
  • 20 Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med 2013; 126 (09) 832.e13-832.e21
  • 21 Raskob GE, Angchaisuksiri P, Blanco AN. , et al; ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost 2014; 40 (07) 724-735
  • 22 Silverstein RL, Bauer KA, Cushman M, Esmon CT, Ershler WB, Tracy RP. Venous thrombosis in the elderly: more questions than answers. Blood 2007; 110 (09) 3097-3101
  • 23 Engbers MJ, van Hylckama Vlieg A, Rosendaal FR. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost 2010; 8 (10) 2105-2112
  • 24 Konstantinides SV, Meyer G, Becattini C. , et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
  • 25 Bates SM, Jaeschke R, Stevens SM. , et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl): e351S-e418S
  • 26 Righini M, Bounameaux H, Perrier A. Effect of age on the performance of single detector helical computed tomography in suspected pulmonary embolism. Thromb Haemost 2004; 91 (02) 296-299
  • 27 Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120 (04) c179-c184
  • 28 Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000; 109 (05) 357-361
  • 29 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
  • 30 Castellucci LA, Cameron C, Le Gal G. , et al. Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis. JAMA 2014; 312 (11) 1122-1135
  • 31 Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124 (15) 2450-2458
  • 32 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
  • 33 Rodger MA, Le Gal G, Anderson DR. , et al; REVERSE II Study Investigators. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ 2017; 356: j1065
  • 34 Tosetto A, Iorio A, Marcucci M. , et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10 (06) 1019-1025
  • 35 Eichinger S, Heinze G, Kyrle PA. D-dimer levels over time and the risk of recurrent venous thromboembolism: an update of the Vienna prediction model. J Am Heart Assoc 2014; 3 (01) e000467
  • 36 Lauber S, Limacher A, Tritschler T. , et al. Predictors and outcomes of recurrent venous thromboembolism in elderly patients. Am J Med 2018; 131 (06) 703.e7-703.e16
  • 37 Tritschler T, Aujesky D. Venous thromboembolism in the elderly: a narrative review. Thromb Res 2017; 155: 140-147
  • 38 Kooistra HA, Calf AH, Piersma-Wichers M. , et al. Risk of bleeding and thrombosis in patients 70 years or older using vitamin K antagonists. JAMA Intern Med 2016; 176 (08) 1176-1183
  • 39 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (05) 1093-1100
  • 40 Fang MC, Go AS, Chang Y. , et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58 (04) 395-401
  • 41 O'Brien EC, Simon DN, Thomas LE. , et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J 2015; 36 (46) 3258-3264
  • 42 Gage BF, Yan Y, Milligan PE. , et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151 (03) 713-719
  • 43 Hijazi Z, Oldgren J, Lindbäck J. , et al; ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 2016; 387 (10035): 2302-2311
  • 44 Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115 (21) 2689-2696
  • 45 Poli D, Antonucci E, Marcucci R. , et al. Risk of bleeding in very old atrial fibrillation patients on warfarin: relationship with ageing and CHADS2 score. Thromb Res 2007; 121 (03) 347-352
  • 46 Peeterbroeck J, Danguy C, Lelubre C, Meulemans M, Higuet S. Bleeding complications with oral anticoagulants in the elderly: an observational study. Geriatr Psychol Neuropsychiatr Vieil 2016; 14 (04) 406-412
  • 47 O'Brien EC, Holmes DN, Thomas L. , et al. Therapeutic strategies following major, clinically relevant nonmajor, and nuisance bleeding in atrial fibrillation: findings from ORBIT-AF. J Am Heart Assoc 2018; 7 (12) e006391
  • 48 Yung D, Kapral MK, Asllani E, Fang J, Lee DS. ; Investigators of the Registry of the Canadian Stroke Network. Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: the Best Practice for Reinitiating Anticoagulation Therapy After Intracranial Bleeding (BRAIN) study. Can J Cardiol 2012; 28 (01) 33-39
  • 49 Qureshi W, Mittal C, Patsias I. , et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol 2014; 113 (04) 662-668
  • 50 Hansen ML, Sørensen R, Clausen MT. , et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170 (16) 1433-1441
  • 51 Ray WA, Chung CP, Murray KT. , et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA 2018; 320 (21) 2221-2230
  • 52 Frey PM, Méan M, Limacher A. , et al. Physical activity and risk of bleeding in elderly patients taking anticoagulants. J Thromb Haemost 2015; 13 (02) 197-205
  • 53 Tomaselli GF, Mahaffey KW, Cuker A. , et al. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017; 70 (24) 3042-3067
  • 54 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. ; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
  • 55 Pollack Jr CV, Reilly PA, Eikelboom J. , et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373 (06) 511-520
  • 56 Connolly SJ, Milling Jr TJ, Eikelboom JW. , et al; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016; 375 (12) 1131-1141
  • 57 Staerk L, Fosbøl EL, Lamberts M. , et al. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 2018; 39 (19) 1698-1705a
  • 58 Nielsen PB, Larsen TB, Skjøth F, Gorst-Rasmussen A, Rasmussen LH, Lip GY. Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation 2015; 132 (06) 517-525
  • 59 Murthy SB, Gupta A, Merkler AE. , et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke 2017; 48 (06) 1594-1600